1. Field of the Invention
This invention is directed to new 1-[(aminooxy)-methyl]-6-substituted-4H-s-triazolo[4,3-a][1,4]benzodiazepin es, intermediates, and the processes of production thereof.
The novel compounds and the processes of the production therefor can be illustratively represented as follows: ##STR3## and if R' and/or R" is of 2 or 3 carbon atoms, inclusive, 2,6 ##STR4## wherein R' and R" are alkyl of 1 to 3 carbon atoms, inclusive; wherein R'" corresponds to R' or R" with the proviso that R" or R' has 2 or 3 carbon atoms, inclusive; wherein R.sub.1 is hydrogen, fluoro, chloro, bromo, nitro, trifluoromethyl or alkylthio in which the alkyl moiety is of 1 to 3 carbon atoms, inclusive; and wherein R.sub.2 is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6 -difluorophenyl, or 2-pyridyl.
Compound IIIB is produced from IV if R' and R" are methyl, if R' and/or R" are alkyl of 2 to 3 carbon atoms, then simultaneously with IIIB compound V is obtained.
Compounds of formula VA: ##STR5## wherein R.sub.1 and R.sub.2 are defined as herein above and wherein R.sub.o is hydrogen or alkyl of 1 to 3 carbon atoms, inclusive; can also be prepared by reacting compound I with a hydroxyamine of the formula: ##STR6##
The invention also embraces the pharmacologically acceptable addition salts of the compounds IIIA and IIIB as well as those of compounds IV, V and VA and the Schiff's bases derived from compound IIIA having the formula VI: ##STR7## wherein R.sub.1 and R.sub.2 are defined as above and R.sub.5 and R.sub.6 are hydrogen or alkyl as defined above.
Thus the invention comprises compounds of formula III (composite formula of IIIA and IIIB): ##STR8## wherein R'.sub.o and R".sub.o are hydrogen or alkyl of 1 to 3 carbon atoms, inclusive; R.sub.1 is hydrogen, fluoro, chloro, bromo, nitro, trifluoromethyl, or alkylthio in which the alkyl moiety is of 1-3 carbon atoms, inclusive; R.sub.2 is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl or 2-pyridyl, and the pharmacologically acceptable acid addition salts thereof.
The invention further comprises the Schiff's bases of formula VI, the hydroxyamines of formulae V and VA and the intermediates of formula IV as well as the pharmacologically acceptable acid addition salts of compounds of formulae IV, V, VA, and VI.
The invention also comprises the processes of production for compounds III, IV, V, VA, and VI.
The process to produce the compounds of formula IIIA (i.e. compounds of formula III, wherein R'.sub.o and R".sub.o are both hydrogen) comprises: treating a compound of formula I with N-hydroxyphthalimide in the presence of a tertiary amine base at 0.degree. to 100.degree. C. to obtain compound II; and treating compound II with hydrazine or its hydrate between 25.degree.-100.degree. C. to obtain compound IIIA.
The process to produce the compounds of formula IIIB (i.e. compounds of formula III, wherein R'.sub.o and R".sub.o are alkyl of 1 to 3 carbon atoms, inclusive) comprises: treating compound I with a N,N-dialkylhydroxyamine and an acid neutralizing agent at 25.degree. to 100.degree. C. to obtain compound IV; heating compound IV between 140.degree. to 200.degree. C. to obtain compound IIIB, and if R' and/or R" is ethyl, propyl, or isopropyl, compound V.
Compounds of formula VA (compounds of formula V in which R'" is also hydrogen) are prepared by condensing a compound of formula I with an unsubstituted or N-monoalkylhydroxyamine.
The process to produce the compounds of formula VI comprises: condensing a compound of formula IIIA with an aldehyde or keto compound at temperatures of 0.degree. to 100.degree. C.